MNK2

Courtesy of Getty Image Although it seems like science fiction, we may one day be able to grow replacement organs and tissues. Our ability to manipulate stem cells is accelerating, and new research places that goal much closer. For that and more reach news, continue reading. New Stem Cell Research Could Lead to Growing Organs in a Petri Dish Research has come a long way in manipulating stem cells in the last decade or two. In theory, it would be possible to use stem cells to grow into whatever type of tissue — even organs — you want. Recent research out of the University of Copenhagen has identified a new step in the development process that puts them one step closer to making that possible. The research was published in the journal Nature Cell Biology. “Very simply put, a number of recent studies have attempted to make a gut from stem cells in a dish,” Martin Proks, a Ph.D. student at the University of Copenhagen and one of the primary authors from Novo Nordisk Foundation Center for Stem Cell Medicine at the university said. “We have found a new way to do this, a way which follows different aspects of what happens in the embryo. Here, we found a new route that the embryo uses, and we describe the intermediate stage that different types of step cells could use to make the gut and other organs.” They evaluated pluripotent stem cells and endoderm extra-embryonic stem cells. The extra-embryonic endoderm cells are a new stem cell line described a few years ago that contributes to the gut organs. They act as support cells that provide membrane nourishment. Using the newly identified “alternative route,” they took extra-embryonic endoderm stem cells and developed them into intestinal organ-like structures in a dish. This new alternative process allows them actually to form organoid structures. To do this, they created a new computational tool that compared clusters of cells that were candidates to form organs associated with the digestive tract, including the liver, pancreas, lung and intestine. They are still having challenges maturing the cells into fully functioning organs, but the findings offer new approaches. Molecule that Stimulates the Formation of New Insulin-Producing Cells Researchers at Karolinska Institute identified and tested a small molecule that can stimulate the regeneration of insulin-producing beta cells. They demonstrated this in zebrafish and mammalian tissue. They believe it has the potential to be a new target for treating diabetes. The molecule binds to a protein called MNK2, regulates mRNA translation and boosts protein synthesis. In both zebrafish and pig tissue, they demonstrated that it could induce the formation of new pancreatic beta cells and stimulate the expression of insulin in human organoids. Dark Matter of the Genome Mutations Linked to Cancer For a long time, non-coding sections of the genome were dubbed “junk DNA” because they didn’t understand what it did. Then they discovered that much of it played a role in regulating gene activity. Now, researchers with Dana-Farber Cancer Institute are finding a link between non-coding mutations and cancer risk. They found that in many cases, mutations in non-coding parts of the genome have an epigenetic effect, which is to say, they change how tightly the DNA at those locations is wrapped. That affects the ability of other segments of DNA or specific proteins to bind to those locations, which influence cancer genes. For example, more than 300 mutations have been identified linked to an increased risk of breast cancer. But less than 10% are within genes, and the rest are in non-coding regions. From their research, they developed a database of mutations that can be linked to cancer risk via a known biological mechanism. Molecule in Mosquito Spit is New Target for Several Diseases Investigators with the University of Leeds identified a molecule in mosquito spit called sialokinin that might be a new target for vaccination against various diseases, including Yellow Fever, Dengue and Zika. Sialokinin makes it easier for several types of viruses to move from mosquitoes to humans. Previous research found that sialokinin could alter the function of blood vessel cells grown in a Petri dish, which allowed for increased blood flow and more effective mosquito feeding. The molecules make blood vessels more permeable, allowing contents to leak out into the skin, which helps viruses infect cells. They also found that sialokinin isn’t found in all mosquitoes’ spit, such as Anopheles, the dominant vector for transmission of malaria, a parasite. These mosquitos cannot spread most viruses. Multiple Heart Conditions Associated with Triple the Dementia Risk A large study out of the University of Exeter and Oxford University evaluated data from more than 200,000 people 60 years or older of European ancestry in the UK Biobank. They identified people diagnosed with cardiometabolic disorders such as diabetes, stroke, a heart attack, or any combination of the three and who went on to develop dementia. They found that the more people had these three conditions, the higher the risk of dementia. People with all three were three times more likely to develop dementia compared to people with a high genetic risk of dementia. They published the research in The Lancet Healthy Longevity. “Dementia is a major global issue, with predictions that 135 million worldwide will have the devastating condition by 2050,” Dr. Xin You Tai, lead author and doctoral student at the University of Oxford, said. “We found that having such heart-related conditions is linked to dementia risk to a greater extent than genetic risk. So whatever genetic risk you were born with, you can potentially make a big impact on reducing risk of dementia by looking after heart and metabolic health throughout life.”

Researchers show how a molecule that they have identified stimulates the formation of new insulin-producing cells in zebrafish and mammalian tissue, through a newly described mechanism for regulating protein synthesis. Researchers at Karolinska Institutet in Sweden show how a molecule that they have identified stimulates the formation of new insulin-producing cells in zebrafish and mammalian tissue, through a newly described mechanism for regulating protein synthesis. The results are published in Nature Chemical Biology. "Our findings indicate a new potential target for treating diabetes, in that we demonstrate a possible way of stimulating the formation of new insulin-producing cells," says the study's last author Olov Andersson, senior researcher at the Department of Cell and Molecular Biology at Karolinska Institutet. Both type 1 and type 2 diabetes are characterised by raised levels of blood sugar, the result of low levels of endogenous insulin, the hormone needed for glucose uptake from the blood, or a physiological inability to utilise the insulin secreted -- or both. Insulin injections and glucose-lowering drugs can control the disease, but not cure it. Regeneration of pancreatic β cells "One alternative could be a treatment that regulates blood glucose by increasing the number of insulin-producing pancreatic β cells, so we're researching the possible regeneration of these cells," says the study's first author Christos Karampelias, former doctoral student at the Department of Cell and Molecular Biology at Karolinska Institutet. The team from Karolinska Institutet has previously identified a small molecule able to stimulate the regeneration of insulin-producing β cells. This they did by analysing a large quantity of substances in a zebrafish model. In this present study, they examined the molecular mechanism of this stimulation. By analysing a large number of molecular interactions in yeast cells, the researchers show that their molecule binds to a protein called MNK2. Subsequent studies of zebrafish and cell cultures indicate that the molecule operates by regulating the translation of mRNA and boosting the synthesis of proteins, without which the formation of new β cells cannot be increased. Zebrafish given the molecule also showed lower levels of blood glucose than controls. The study also shows that the molecule can induce the formation of new pancreatic β cells from pigs and stimulate the expression of insulin in human organoids (organ-like cell formations). Studies of human tissue "We'll now be studying the effect of this and similar molecules in human tissue and analysing the molecule's target protein, MNK2, in tissue from healthy donors and donors with diabetes," says Dr Andersson. The studied molecule was found through studies on zebrafish, providing a valuable model for testing a large number of potential diabetes drug candidates. Since the fish embryo is transparent, its development is easy to monitor with a microscope. Zebrafish larvae also have only one cluster of β cells, a so-called islet of Langerhans, which facilitates studies of how new β cells are formed after the population have been decreased in a way that mimics the onset of type 1 diabetes. The study was financed by the European Research Council, the Swedish Research Council, the Ragnar Söderberg Foundation, the Novo Nordisk Foundation, the Strategic Research Programme in Diabetes (SRP Diabetes) and the Strategic Research Area in Stem Cell Research and Regenerative Medicine (StratRegen) at Karolinska Institutet.

SAN DIEGO, July 16, 2021 (GLOBE NEWSWIRE) --eFFECTOR Therapeutics, Inc., , a leader in the development of selective translation regulation inhibitors (“STRIs”) for the treatment of cancer, announced today the publication of data highlighting the role of eukaryotic translation initiation factor 4E (“eIF4E”), in the peer-reviewed journal Cell Reports. eIF4E is a component of the eIF4F complex, which, in conjunction with its activating kinase (“MNK”), triggers an increase in protein synthesis that is critical for cancer growth and immune evasion. The published research, which provides insight into the potential of eIF4E inhibition for the treatment of cancer, was conducted at the University of California, San Francisco in collaboration with eFFECTOR. The eIF4E target is the subject of eFFECTOR’s collaboration with Pfizer. “This publication further validates the novel science on which eFFECTOR’s platform is built,” said Steve Worland, Ph.D., president and CEO of eFFECTOR. “These findings underscore eIF4E’s role as a key hub for regulating cancer drivers such as mitochondrial stress, and the data showed that jointly inhibiting Bcl-xL while blocking eIF4E activation using our MNK 1/2 inhibitor tomivosertib is a promising approach for treating cancer.” “The results in this paper highlight the numerous genetic interactions with eIF4E that may help inform cancer vulnerabilities,” said Davide Ruggero, Ph.D., senior author on the paper; professor at the UCSF Helen Diller Cancer Center; an American Cancer Society Research Professor; and co-founder of eFFECTOR. “Our team is pleased to add to the growing body of scientific research on the interactions between cellular processes that drive cancer and key components of the translation machinery such as eIF4E. We are proud that our contributions have the potential to broaden the treatment landscape for those impacted by cancer.” The Role of eIF4E in Cancer eIF4E is an oncogene and historically intractable target that is activated in a variety of human cancers and is linked to poor prognosis and resistance to certain therapies. eIF4E is an effector protein integrating signals from multiple important oncogenes and tumor suppressor proteins in the PI3K and RAS oncogenic pathways (including PI3K, AKT, mTOR, PTEN and BRAF), and selectively regulates the translation of a set of target mRNA distinct from those regulated by MNK1/2 and eIF4A. This may expand the potential patient population that may benefit from translation regulation therapy. About Tomivosertib (eFT508) Tomivosertib is eFFECTOR’s wholly-owned, highly selective translation regulation inhibitor that targets MNK1 and MNK2 (MNK1/2). The oral, small molecule drug candidate has been shown to enhance killing of tumor cells by T cells, delay T-cell exhaustion/dysfunction and enhance the T-cell central memory pool, in part by down-regulating multiple checkpoint proteins including PD-1, PD-L1, TIM-3 and LAG-3. Tomivosertib is being evaluated in KICKSTART, eFFECTOR’s randomized, double-blind, placebo-controlled Phase 2b study in non-small cell lung cancer (“NSCLC”) in combination with pembrolizumab. The KICKSTART trial builds on results obtained in an earlier study of tomivosertib as an extension of checkpoint inhibitor treatment in patients experiencing insufficient response to an FDA-approved checkpoint inhibitor alone. Please visit for further information on ongoing clinical trials of tomivosertib. About eFFECTOR Therapeutics eFFECTOR is a clinical-stage biopharmaceutical company focused on pioneering the development of a new class of oncology drugs referred to as selective translation regulator inhibitors. eFFECTOR’s STRI product candidates target the eIF4F complex and its activating kinase, mitogen-activated protein kinase 1/2 (MNK 1/2). The eIF4F complex is a central node where two of the most frequently mutated signaling pathways in cancer, the PI3K-AKT and RAS-MEK pathways, converge to activate the translation of select mRNA into proteins that are frequent culprits in key disease-driving processes. Each of eFFECTOR’s product candidates is designed to act on a single protein that drives the expression of multiple functionally related proteins, including oncoproteins and immunosuppressive proteins in T cells, that together control tumor growth, survival and immune evasion. eFFECTOR’s lead product candidate, tomivosertib, is a MNK 1/2 inhibitor, currently being evaluated in KICKSTART, a randomized, double-blind, placebo controlled Phase 2b trial of tomivosertib in combination with pembrolizumab in patients with metastatic NSCLC. Zotatifin, eFFECTOR’s inhibitor of eIF4A, is currently in the dose-escalation portion of a Phase 1/2 trial, with Phase 2a expansion cohorts expected to initiate in the second half of 2021. eFFECTOR has a global collaboration with Pfizer to develop inhibitors of a third target, eIF4E. eFFECTOR plans to evaluate zotatifin as a potential host-directed anti-viral therapy in patients with mild to moderate COVID in collaboration with the University of California, San Francisco, under a $5 million grant sponsored by the Defense Advanced Research Projects Agency. Additional Information and Where to Find It On May 26, 2021, eFFECTOR entered into a definitive Agreement and Plan of Merger (the “Merger Agreement”) with Locust Walk Acquisition Corp. (NASDAQ: LWAC), a special purpose acquisition company, and Locust Walk Merger Sub, Inc., a wholly owned subsidiary of LWAC. In connection with the Merger Agreement, LWAC has filed a registration statement on Form S-4 with the SEC, which includes a document that will serve as a prospectus and proxy statement of LWAC, referred to as a proxy statement/prospectus. A proxy statement/prospectus will be sent to all LWAC stockholders. LWAC also will documents regarding the Merger Agreement and the transactions contemplated thereby (the “Transactions”) with the SEC. Before making any voting decision, investors and security holders of LWAC are urged to read the registration statement, the proxy statement/prospectus and all other relevant documents filed or that will be filed with the SEC in connection with the Transactions as they become available because they will contain important information about the Transactions, including the terms of the Transactions, the parties involved and the risks associated with the Transactions. Investors and security holders will be able to obtain free copies of the registration statement, the proxy statement/prospectus and all other relevant documents filed or that will be filed with the SEC by LWAC through the website maintained by the SEC at Alternatively, these documents, when available, can be obtained free of charge from LWAC upon written request to Locust Walk Acquisition Corp., c/o eFFECTOR, 11120 Roselle Street, Suite A, San Diego, CA 92121, Attn: Secretary, or by calling (858) 925-8215. Participants in the Solicitation LWAC and eFFECTOR and their respective directors and executive officers may be deemed to be participants in the solicitation of proxies from LWAC’s stockholders in connection with the Transactions. A list of the names of the directors and executive officers of LWAC and information regarding their interests in the Transactions will be contained in the proxy statement/prospectus when available. You may obtain free copies of these documents as described in the preceding paragraph. No Offer or Solicitation This communication does not constitute an offer to sell or the solicitation of an offer to buy any securities or a solicitation of any vote or approval, nor shall there be any sale of any securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of such other jurisdiction. Forward-Looking Statements This press release contains certain forward-looking statements within the meaning of the federal securities laws. All statements other than statements of historical facts contained in this press release, including statements regarding the potential that inhibition of eIF4E could broaden the treatment landscape for cancer patients, and the proposed business combination of eFFECTOR and LWAC, are forward-looking statements. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to: potential delays in the commencement, enrollment and completion of clinical trials; disruption to eFFECTOR’s operations from the COVID-19 pandemic, including delaying or otherwise disrupting its clinical trials, manufacturing and supply chain; eFFECTOR’s dependence on third parties in connection with product manufacturing and clinical testing; the results of preclinical studies and early clinical trials are not necessarily predictive of future results; the success of eFFECTOR’s clinical trials and preclinical studies for its product candidates; unexpected adverse side effects or inadequate efficacy of eFFECTOR’s product candidates that may limit their development, regulatory approval and/or commercialization, or may result in recalls or product liability claims; risks relating to the proposed business combination, including the risk that the transaction may not be completed in a timely manner or at all; and the risks associated with eFFECTOR’s business and the business combination set forth in the Appendix to the investor presentation filed as Exhibit 99.3 to the Current Report on Form 8-K filed by LWAC on May 27, 2021 . Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond LWAC’s and eFFECTOR’s control, you should not rely on these forward-looking statements as predictions of future events. The foregoing list of factors is not exclusive, and you should carefully consider the foregoing factors and the other risks and uncertainties described in the “Risk Factors” section of LWAC’s Annual Report on Form 10-K for the year ended December 31, 2020 filed with SEC on March 29, 2021, the registration statement on Form S-4 discussed above and other documents filed by LWAC from time to time with the SEC. These filings identify and address other important risks and uncertainties that could cause actual events and results to differ materially from those contained in the forward-looking statements, including the risk that the conditions under the Merger Agreement are not satisfied. Forward-looking statements speak only as of the date they are made. Readers are cautioned not to put undue reliance on forward-looking statements, and except as required by law. LWAC and eFFECTOR assume no obligation and do not intend to update or revise these forward-looking statements, whether as a result of new information, future events, or otherwise. Neither LWAC nor eFFECTOR gives any assurance that either LWAC or eFFECTOR or the combined company will achieve its expectations. Contacts: Investors: Stephanie Carrington Westwicke, an ICR Company 646-277-1282 Stephanie.Carrington@westwicke.com Media: Heidi Chokeir, Ph.D. Canale Communications 619-203-5391 heidi.chokeir@canalecomm.com